The first visible signs of aging are usually found on the skin: dryness, fine lines and wrinkles, age spots, red blotches, sagging and flaccid skin. Dullness and loss of hair are also well-known symptoms. Numerous skin or hair care products are available to consumers for treatment or prevention of these skin conditions that are caused by various external sources of stress, including, without limitation, atmospheric pollution, mechanical stress, contact with household and other chemicals and sun exposure (photoaging) including sunburns. This is of course in addition to natural stresses such as acne, diet and general aging.
Skin is perpetually exposed to these stresses, which result in visible signs of skin aging and damage, such as wrinkling and dryness, thinning of the skin and other histological changes. As the skin ages, there is a reduction in protein synthesis, an increase in proteolysis and a general disruption of the skin barrier, connective tissue and cohesion.
Many compounds have been described as being useful for improving skin appearance and physiology, including reducing fine lines, wrinkles and other symptoms associated with aged or photodamaged skin. Many compositions are available on the world wide market. But improvement is always desirable.
Retinoids, alpha and beta-hydroxy acids, flavonoids and Isoflavones are proposed to act against acne and wrinkles, to speed cell renewal, to correct hormonal imbalances. These remedies are not without problems, such as instability (retinoids, flavonoids), irritation (retinoids, hydroxyacids) and potential side effects (phytoflavones).
International Patent Appln. No. WO 00/43,417, published Jul. 27, 2000, assigned to SEDERMA, discloses the use of certain peptides and derivatives as cosmetics or pharmaceutical compositions for the regulation of impaired immunologic functions and inflammation of the skin. The peptides and derivatives described have between 2 and 5 amino acids in length. These peptides and derivatives are said to act by reducing the tissue concentrations of IL-6 and IL-8 to levels close to those observed in young tissues. Exemplified peptides include N-Palmitoyl-Pro-Arg, N-Palmitoyl-Thr-Lys-Pro-Arg (SEQ ID NO: 1), Arg-Lys-Pro-Arg (SEQ ID NO: 2) and N-Palmitoyl-Gly-Gln-Pro-Arg (SEQ ID NO: 3). While combinations of various peptides in accordance with WO 00/43,417 are possible, the reference does not specifically identify a combination of a tripeptide and a tetrapeptide. See also U.S. Pat. Nos. 6,620,419 and 6,492,326 disclosing cosmetic and personal care product incorporating, inter alia, certain tetrapeptides.
SEDERMA also sells a product under the trade name EYELISS to treat bags under the eyes. This product includes a mixture of N-PalmitoylGly-Gln-Pro-Arg (SEQ ID NO: 3) and the dipeptide Val-Trp. This dipeptide has no significant collagen stimulating activity and the combination does not exhibit any enhancement in this property over the levels realized by the use of the tetrapeptide alone. See also JP 07/324,097 and JP 08/311,098 to Daicel Chem, Ind. Ltd., as well as Kawamoto Takafumi et al., Chemical Abstracts, Vol. 124, No. 19, 6 May 1996 (Abstract No. 261765).